Emerging optical techniques such as high-resolution microendoscopy (HRME) are currently being examined for their reliability in discriminating benign from neoplastic epithelium. These techniques may offer the potential to detect the margin of an upper aerodigestive tract tumour in a non-invasive manner, allowing targeted biopsy, and even margin control during resection. Research is currently at an early stage. HRME entails the topical application of proflavine as a fluorescent contrast agent, followed by the use of a fibreoptic probe, placed on the mucosal surface, which transmits an image to a tablet device. The authors of this study conducted a feasibility study to determine the sensitivity and specificity of HRME. Multiple blinded reviewers evaluated HRME images of patients with squamous cell carcinoma, with sensitivity and specificity of 96% and 95% respectively compared to gold-standard histopathology. Real-time interrogation of tissue to detect malignancy is an exciting emerging field. The technology reviewed in this article is however currently hampered by the ability only to examine very superficial tissues, and artefacts created by inflammation, keratin debris, bleeding and other factors.